Ray Kausik K, Cannon Christopher P
TIMI Study Group, Cardiovascular Division, Department of Medicine Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Curr Opin Lipidol. 2004 Dec;15(6):637-43. doi: 10.1097/00041433-200412000-00003.
The results of a landmark clinical study comparing intensive statin therapy with conventional statin therapy, in patients with acute coronary syndromes (ACS), are reviewed. The mechanisms behind these results are analysed drawing data from vascular and cell biology.
The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) study showed that intensive statin therapy with 80 mg of atorvastatin to achieve a low-density lipoprotein cholesterol of 62 mg/dl resulted in a 3.9% absolute and a 16% relative risk reduction in death or major cardiovascular events up to 2 years, compared to 40 mg of pravastatin, in patients with ACS. The results were especially significant as intensive statin therapy resulted in a very early benefit (<30 days) and occurred against a background of percutaneous coronary intervention (69%) for the index admission and high use of medications for secondary prevention. The PROVE IT and the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) C-reactive protein sub-study also showed that atorvastatin (80 mg) resulted in a significant reduction in markers of inflammation, whilst the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study showed that intensive statin therapy was associated with reduced progression of atherosclerosis compared with conventional doses of statins.
Intensive statin therapy results in a significant early reduction in adverse cardiac events in ACS patients which are sustained over 2 years. The early benefits seen are likely to result from modulation of inflammation, endothelial function and coagulation, i.e. the pleiotropic effects, whereas the greater reduction in low-density lipoprotein cholesterol results in reduced long-term events.
回顾一项具有里程碑意义的临床研究结果，该研究比较了急性冠状动脉综合征（ACS）患者强化他汀治疗与常规他汀治疗的效果。从血管生物学和细胞生物学数据中分析这些结果背后的机制。
普伐他汀或阿托伐他汀评估与感染治疗-心肌梗死溶栓（PROVE IT-TIMI 22）研究表明，在ACS患者中，与40mg普伐他汀相比，使用80mg阿托伐他汀进行强化他汀治疗以使低密度脂蛋白胆固醇达到62mg/dl，可使2年内死亡或主要心血管事件的绝对风险降低3.9%，相对风险降低16%。这些结果尤为显著，因为强化他汀治疗在非常早期（<30天）就带来了益处，且是在首次入院接受经皮冠状动脉介入治疗（69%）以及大量使用二级预防药物的背景下出现的。PROVE IT研究和积极降低胆固醇减少心肌缺血（MIRACL）C反应蛋白亚研究还表明，阿托伐他汀（80mg）可显著降低炎症标志物水平，而积极降脂逆转动脉粥样硬化（REVERSAL）研究表明，与常规剂量他汀相比，强化他汀治疗与动脉粥样硬化进展减缓有关。
强化他汀治疗可使ACS患者的不良心脏事件在早期显著减少，并持续2年以上。早期出现的益处可能源于炎症、内皮功能和凝血的调节，即多效性作用，而低密度脂蛋白胆固醇的更大降低则导致长期事件减少。
